Drug Loading Procedures

Johnsson M, Bergstrnd N, Edwards K. Optimization of drug loading procedures and characterization of liposomal formulations of two novel agents intended for boron neutron capture therapy (BNCT). J Liposome Res 1999 9 53-79. 

Aliabadi and Lavasanifar (2006) recently reviewed some pharmaceutical examples of drugs loaded into polymeric micelles as well as the corresponding drug loading procedures. Polymeric micelle... 

Fournier, E. Dufresne, M.H. Smith, D.C. Ranger, M. Leroux, J.C. A novel one-step drug-loading procedure for water-soluble amphiphilic nanocarriers. Pharm. Res. 2004, 21, 962-968. 

The drug loading capacity and drug release kinetics are affected by several factors such as the adsorptive properties of the mesoporous materials (e.g., pore size, surface area, pore volume) [35, 36, 52, 55], surface functionalization of the mesoporous materials [37b, 51b, 56, 57], and the drug loading procedures used (e.g., covalent attachment, physical trapping, and adsorption) [58]. These will be discussed individually below. 

Figure 4.8. Most often used drug-loading procedures simple equilibrium (a), dialysis (b), oil-in-water emulsion (c), solution casting (d) and freeze-drying (e).[Reproduced from Dufresne et al]. ...

E Allemann, JC Leroux, R Gurny, E Doelker. In vitro extended-release properties of drug loaded poly (dl-lactic acid) nanoparticles produced by a salting-out procedure. Pharm Res 10(12) 1732—1737, 1993. 

Both nanospheres and nanocapsules are prepared from either a polymerization reaction of dispersed monomers or from a solvent dispersion procedure using preformed polymers. In many instances, the latter procedure using preformed polymer is desirable, as potential reactions between drug and monomer are avoided and the potential toxicity of residual monomers, surfactant, and initiator is reduced [37], The final properties of nanoparticles, such as their size, morphology, drug loading, release characteristics, and biodisti-bution, are all influenced by the method of preparation [38],... 

The injeetion method and reverse phase dialysis are additional procedures for the formation of SUV and LUV. Freeze-thaw procedures allow drug loading of the liposomes and offer an evaluation of the stability of the vesieular dispersion. For further reading. Refs. 7 and 8 are recommended. 

In spite of a rapidly increasing amount of literature data on drug-loaded solid lipid nanoparticle dispersions, there is comparatively little systematic knowledge about the interaction of drugs with these complex systems (e.g., with respect to the state and localization of the drug within the dispersions). One reason may be that the type of interaction is expected to be quite specific for each drug/particle matrix combination, and this interaction may also depend on the general composition of the dispersion and the preparation procedure. 

The above procedure was also employed to investigate buccal absorption from the HEMAC experimental delivery device. As in the case of the diffusion cell the drug-loaded disc was positioned on the inner central surface of the buccal mucosa. An impermeable film coated with mucosal adhesive (F-4000, Adhesives Research, Glen Rock, PA) on the periphery was then positioned over the HEMAC disc to prevent dehydration and to secure the device in place on the mucosal surface. The disc was allowed to remain in contact with the mucosa for 4 h before it was removed for quantitation of residual drug content. Blood samples were collected over the same interval as for the saturated solution and processed in the same manner. 

Several methods have been developed for preparing nanoparticles and are optimized on the basis of their physicochemical properties (e.g., size and hy-drophilicity) with regard to their in vivo fate after parenteral administration. The selection of the appropriate method for preparing drug-loaded nanoparticles depends on the physicochemical properties of the polymer and the drug. On the other hand, the procedure and the formulation conditions will determine the inner structure of these polymeric colloidal systems. Two types of systems with different inner structures are possible ... 

The following chapter introduces a remote loading procedure for anthracyclines focussing on the well-established drug doxorubicin. 

An optimal loading procedure for doxorubicin into liposomes aims at a high drug to lipid ratio and an encapsulation efficiency of almost 100% to render the separation of unencapsulated drug unnecessary. 

The remote loading procedure consists of three steps preparation of the liposomes, establishment of an ion-gradient and loading of the drug into the preformed liposomes (Fig. 2). 

The second discovery that enabled liposomes to be developed into efficacious anticancer drug delivery systems was the development of an efficient loading procedure that resulted in liposomes with high drug concentrations. This in turn permitted a reduction in the amount of phospholipid to be administered concomitantly with a given drug dose. This advanced technique was developed during formulation studies on doxorubicin that eventually led to a liposomal formulation that is now licensed as Caelyx for the treatment of Kaposi s sarcoma and ovarian cancer. 

Lipospheres have successfully been used to deliver a variety of substances, among them peptide drugs. Lipospheres seem to fulfill the basic requirements of a carrier for drug delivery. A sufficient drug load can be achieved, depending on the incorporation methods. Attempts have been made to investigate procedures, limiting 2005 by CRC Press LLC... 

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